Diabetes is a major cause of morbidity and mortality in the United States and throughout the world. Diabetes is a metabolic disease characterized by the inability to metabolize glucose and generally divided into two types. Of the two types, type 1 diabetes usually results from autoimmune destruction of beta cells in the pancreas during adolescence which leads to insufficient insulin production.
Research into the causes and treatments for type 1 diabetes frequently involve the use of nonhuman animals. The non-obese diabetic (NOD) mouse is one animal model system generally accepted for studying type 1 diabetes as NOD mice develop a form of diabetes that parallels type 1 diabetes in humans, including sharing common susceptibility factors such as major histocompatibility complex molecules. Studies of NOD mice and humans have indicated that two proteins synthesized by pancreatic beta cells play determining roles as autoantigens responsible for the onset of diabetes. The two proteins are the hormone insulin, a secreted protein, and the enzyme glutamic acid decarboxylase (GAD), an intracellular protein found as either soluble GAD67, or membrane-bound GAD65 in beta cells. The importance of these two autoantigens for diabetes onset in NOD mice is indicated by the finding that most pathogenic CD8+ T cells recognize a single insulin epitope, and that mice with beta cell-specific reduced expression of gad65/67 genes do not develop diabetes. In humans, the presence of anti-insulin and anti-GAD autoantibodies has been used to predict the onset of diabetes. There remains, however, a need for a method of preventing diabetes in humans.